The long term objective of this research project is to gain a more complete understanding of the role of neuropeptide Y in the neural control of the heart. Abundant stores of neuropeptide Y coexist with norepinephrine in sympathetic nerve terminals throughout the heart, and sympathetic activation evokes the concomitant release of neuropeptide Y and norepinephrine. The specific aims of the proposed experiments are (l) to determine the effects of neuropeptide Y on vagally-induced cardiac chronotropic, inotropic, and dromotropic responses, (2) to determine how the cardiac sympathetic neurons that contain neuropeptide Y are distributed to various functional regions of the heart, and (3) to investigate the factors that modulate the release and removal of neuropeptide Y from the heart. We will assess the inhibitory effect of brief train of sympathetic stimulation on vagally-induced chronotropic, inotropic, and dromotropic responses, before an after we administer adrenergic receptor antagonists. We will monitor the vagally- induced cardiac responses after individually stimulating, the right and left ansae subclaviae, to determine the distribution of neuropeptide Y-containing sympathetic fibers to various structures of the heart. We will stimulate the cardiac sympathetic nerves and compare the overflows of neuropeptide Y and norepinephrine into the coronary sinus blood, during and after the cessation of sympathetic stimulation. We will correlate the overflow of neuropeptide Y in the coronary sinus blood with the effects of neuropeptide Y on vagally-induced cardiac chronotropic responses. We will measure the coronary sinus plasma content of norepinephrine by means of reverse-phase high performance liquid chromatography with electrochemical detection, and we will measure the plasma content of by means of specific radioimmunoassay. We will determine whether vagal stimulation and adrenergic receptor blockade modulate the overflow of neuropeptide Y from sympathetic neurons in a manner similar to the modulation of the overflow of norepinephrine. We will assess the role of neuropeptide Y in suppressing the release of norepinephrine from sympathetic nerve terminals during sustained cardiac sympathetic stimulation. Knowledge of the function of neuropeptide Y in the neural control of the heart is important because neuropeptide Y is released together with norepinephrine from cardiac sympathetic nerve terminals under physiologic conditions. Thus, neuropeptide Y is likely to play a role in the moment to moment regulation of cardiac function by the autonomic nervous system.